tbuckley/cabot-search huggingface dataset:
First-line lenvatinib + pembrolizumab treatment across non-clear cell renal cell carcinomas: Results of the phase 2 KEYNOTE-B61 study.
Authors: Chung-Han Lee, Howard Gurney, Vagif Atduev, Cristina Suárez, Miguel A Climent Duran, David William Pook, Piotr Tomczak, Philippe Barthelemy, Jae-Lyun Lee, Taron Nalbandian, Viktor Stus, Thomas Ferguson, Pawel Wiechno, Erhan Gokmen, Louis Lacombe, Craig Gedye, Joseph Burgents, Manish Sharma, Xiang Peng, Laurence Albiges
Journal: Journal of Clinical Oncology (2023)

4518 Background: Lenvatinib (lenva) + pembrolizumab (pembro) is a first-line treatment for advanced clear cell renal cell carcinoma (RCC). Initial results of the single-arm, phase 2 KEYNOTE-B61 (NCT04704219) study showed antitumor activity of lenva + pembro in patients (pts) with advanced non-clear cell RCC who had opportunity for ≥24 wk of follow-up (n=82). We report results from the complete cohort of pts enrolled in KEYNOTE-B61 (N=158) with extended follow-up. Methods: Adults with previously untreated advanced non-clear cell RCC and measurable disease per RECIST v1.1 received lenva 20 mg PO QD + pembro 400 mg IV Q6W for up to 18 cycles (~2 y). The primary end point was ORR per RECIST v1.1 by blinded independent central review (BICR). Secondary end points included DOR, DCR, and PFS per RECIST v1.1 by BICR; OS; and safety. Histology was assessed by investigator (assessment by central review is planned). Results: Of 158 treated pts, 93 (59%), 29 (18%), and 21 (13%) had papillary, chromophobe, and unclassified histology, respectively. Additionally, 6 pts (4%) had translocation and 9 (6%) had other histology. 70 pts (44%) had IMDC favorable risk and 88 (56%) had intermediate/poor risk. Median follow-up was 14.9 mo (range 8.7-19.7). ORR was 49% (95% CI, 41-57; 9 CRs [6%]; 69 PRs [44%]). DCR was 82% (95% CI, 75-88). Median DOR was not reached (NR; range, 1.5+ to 15.3+ mo). By Kaplan-Meier estimate, 75% of responders had a response for ≥12 mo. ORR and DCR by histology are shown in the table. For the IMDC favorable risk group, ORR was 51% (95% CI, 39-64) and DCR was 87% (95% CI, 77-94). For the IMDC intermediate/poor risk group, ORR was 48% (95% CI, 37-59) and DCR was 78% (95% CI, 68-86). In all pts, median PFS and OS were 17.9 mo (95% CI, 13.5-NR) and NR (95% CI, NR-NR), respectively; 12-mo rates were 63% and 82%. Treatment-related AEs (TRAEs) occurred in 149 pts (94%) and were consistent with results from other studies. The most common (≥30%) TRAEs were hypertension (n=90; 57%), diarrhea (n=69; 44%), and hypothyroidism (n=58; 37%). Grade 3-4 TRAEs occurred in 81 pts (51%). Overall, 17 pts (11%) discontinued pembro, 14 (9%) discontinued lenva, and 5 (3%) discontinued both drugs because of TRAEs. No deaths occurred because of TRAEs. Conclusions: In pts with advanced non-clear cell RCC enrolled in KEYNOTE-B61, lenva + pembro showed antitumor activity with no new safety signals. These data support the use of lenva + pembro as first-line treatment for pts with non-clear cell RCC, regardless of histology. Clinical trial information: NCT04704219 . [Table: see text]
Efficacy and safety of camrelizumab in combination with radiation and chemotherapy for recurrent or metastatic cervical cancer.
Authors: Zhongjie Chen, Bo Yan, Liming Xu, Xin Huang, Meng Li, Jun Wang, Li Zhu, Zhiyong Yuan, Ping Wang
Journal: Journal of Clinical Oncology (2023)

5542 Background: Cisplatin-based concurrent chemoradiation regimens have been suggested to be beneficial in recurrent or metastatic cervical cancer. Immunotherapy has also shown good therapeutic efficacy in recurrent or metastatic cervical cancer. Among them, Pembrolizumab in combination with chemotherapy has been used for first-line treatment of advanced PD-L1-positive cervical cancer. Meanwhile, Camrelizumab has shown good anti-tumor activity and manageable toxicity in patients with locally advanced cervical cancer. The primary objective of this study is to evaluate the efficacy and safety of Camrelizumab in combination with concurrent chemoradiation in patients with recurrent or metastatic cervical cancer. Methods: Patients diagnosed with recurrent or metastatic cervical cancer received Camrelizumab combined with concurrent chemoradiotherapy, radiotherapy:External beam radiotherapy (EBRT) 1.8-2.15 Gy/f, a total of 28 fractions; Brachytherapy: high-risk CTV using image guidance 28 Gy in 4 fractions (18 Gy in 3 fractions for posthysterectomy recurrent patients); chemotherapy regimen used TP regimen (paclitaxel: 175 mg/m 2 , cisplatin: 75 mg/m 2 , Q3W 6 cycles); Camrelizumab 200 mg Q3W 6 cycles. The primary endpoint of this trial was objective response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and incidence of adverse reactions. Results: From September 16, 2020 to September 30, 2022, a total of 29 patients were recruited. 27 of these patients completed 6 cycles of planned treatment. 27 patients had a median age of 53 years (33-73 years), ECOG PS 0 (n = 8), ECOG PS 1 (n = 14), ECOG PS 2 (n = 1). The ORR rate was 96.30% (26/27), including 17 patients with CR, 9 patients with PR, and 1 patient with SD Treatment-related AEs were mainly lymphocyte count decreased, anemia, and white blood cell count decreased, with overall safety manageable and no treatment-related deaths. Conclusions: Camrelizumab combined with concurrent chemoradiation in patients with recurrent or metastatic cervical cancer has good efficacy, low side effects and acceptable toxicity. Clinical trial information: NCT04884906 .
ALTER-UC-007: A prospective phase 2 study of anlotinib with gemcitabine and cisplatin or anlotinib with penpulimab as perioperative treatment for patients with muscle-invasive urothelial carcinoma (MIUC).
Authors: Hailiang Zhang, Yiping Zhu, Ding-Wei Ye
Journal: Journal of Clinical Oncology (2023)

TPS4612 Background: Radical surgery involving cystectomy and nephroureterectomy is the standard of care for patients with localized muscle-invasive urothelial carcinoma (MIUC). In recent years, neoadjuvant- and adjuvant-containing multimodality therapies have gradually been adopted in attempt to eradicate micrometastatic disease and improve the outcomes achieved with radical surgery alone. This study aims to evaluate the efficacy and safety of anlotinib (a multi-target tyrosine kinase inhibitor of angiogenesis) with gemcitabine and cisplatin or anlotinib with penpulimab (a humanized anti-PD-1 IgG1 monoclonal antibody) as neoadjuvant and adjuvant therapy in patients with MIUC. Methods: In this open-label, prospective, phase 2 study, eligible patients include those with histologically confirmed clinical stage T1-T4N1-3M0, T3-4N0M0 MIUC (tumors of the bladder, renal pelvis, ureter and urethra) fit and planned for radical cystectomy, nephroureterectomy or ureterectomy. Main exclusion criteria are distant metastatic disease; prior chemotherapy, anti-angiogenic therapy, radiation therapy or immunotherapies; active autoimmune disease; uncontrolled hypertension or patients at high bleeding risk. Patients will be enrolled and receive treatment based on PD-L1 status in tumor tissue. The PD-L1 status of eligible patients will be centralized and assessed using an anti-PD-L1 antibody and an immunohistochemical (IHC) assay. PD-L1 positivity was defined as combined positive score (CPS) ≥1 (previously reported as and equivalent to CPS ≥1%). The study treatment is stratified into two cohorts based on PD-L1 expression levels. In cohort 1, the PD-L1 negative patients with MIUC will receive neoadjuvant anlotinib (12 mg orally QD D1-14 every 3 weeks) + gemcitabine (1000 mg/m 2 , intravenously [IV] on days 1 and 8) + cisplatin (35 mg/m 2 IV on days 1 and 8) for a maximum of 4 cycles followed by radical surgery and 2 cycles of adjuvant treatment post-surgery. In cohort 2, PD-L1 positive patients will receive anlotinib (12 mg orally QD D1-14 every 3 weeks) + penpulimab (200 mg IV every 3 weeks) for a maximum of 4 cycles followed by radical surgery and 2 cycles of adjuvant treatment post-surgery. After the completion or discontinuation of the study treatment, safety follow-up and survival follow-up will be performed. Tumor imaging was performed by computed tomography (preferred) or magnetic resonance imaging at baseline, and every 6 weeks during treatment, then every 6 months through year 2. Objective response rate (ORR) is the primary endpoint. Secondary endpoints included pathological complete response rate (pCR), disease-free survival (DFS), overall survival (OS) and safety. Recruitment have begun in October 2022. Currently, the study is active with 1 participant has been enrolled. Clinical trial information: ChiCTR2200063085 .
Racial and ethnic disparities in survival among persons with subsequent primary cancer.
Authors: Hyuna Sung, Lauren Nisotel, Ephrem Tadele Sedeta, Farhad Islami, Ahmedin Jemal
Journal: Journal of Clinical Oncology (2023)

12093 Background: Racial and ethnic disparities in survival after first primary cancer diagnoses have been well documented. Yet comprehensive data for disparities after subsequent primary cancer (SPC) are lacking despite the growing burden of SPCs. Methods: This study included 230,370 persons diagnosed with one of the 13 common SPCs at ages≥20 years during 2000-2013 in 18 Surveillance, Epidemiology, and End Results registries. Cause-specific proportional hazards models were used to estimate HR (hazard ratio), overall and stratified by SPC types, comparing the risk of cancer or cardiovascular death in Hispanic, non-Hispanic Asian or Pacific Islander (API), or non-Hispanic Black (Black) persons to that in non-Hispanic White (White) persons. HRs were adjusted for sex, first primary cancer type and stage, age and year of SPC diagnosis (base model); and additionally household income, urbanicity, SPC stage, subtype, and treatment receipt (surgery, radiotherapy, chemotherapy) (final model). Results: During 54 months of median follow-up, 109,757 cancer deaths and 18,283 cardiovascular deaths occurred among persons with SPCs. Overall, HRs for cancer death were higher among Black (HR = 1.21, 95% CI = 1.18-1.23) and Hispanic (HR = 1.10, 95% CI = 1.07-1.13) persons compared with White persons, but lower among API persons (HR = 0.93, 95% CI = 0.90-0.96) in the base model. When stratified by SPC types, the increased HRs were evident for 10 of 13 cancers among Black persons with the greatest HR among those with uterine corpus cancer (HR = 1.87, 95%CI = 1.63-2.15) and for 7 of 13 cancers among Hispanic persons with the highest HR among those with melanoma (HR = 1.46, 95%CI = 1.21-1.76). For cardiovascular death, compared with White persons, the overall HR was higher among Black (HR = 1.42, 95% CI = 1.35-1.49) persons but lower among API (HR = 0.75, 95%CI = 0.69-0.81) and Hispanic (HR = 0.90, 95% CI = 0.84-0.96) persons. The risk of cardiovascular death was higher for 11 of 13 cancers among Black persons with the greatest HR among those with pancreatic (HR = 1.80, 95%CI = 1.17-2.75), thyroid (HR = 1.70, 95%CI = 1.12-2.57), and kidney (HR = 1.63, 95%CI = 1.38-1.93) cancers. Additional adjustments in the final model reduced the elevated HRs substantially especially for cancer death among Black or Hispanic persons, although the associations remained statistically significant for most cancers. Conclusions: Among persons with SPCs, Black persons had a higher risk of death from both cancer and cardiovascular disease, whereas Hispanic persons had a higher risk of death from cancer. Adjusting for differences in potentially modifiable factors attenuated the associations substantially, highlighting opportunities for interventions toward health equities among cancer survivors.
Prognosis and risk of suicide after cancer diagnosis.
Authors: Connor J Kinslow, Prashanth Kumar, Melanie Wall, Holly Gwen Prigerson, Mark Olfson, Lisa A. Kachnic, David Paul Horowitz, James B. Yu, Simon Cheng, Alfred I. Neugut
Journal: Journal of Clinical Oncology (2023)

6634 Background: Suicide rates are elevated acutely after cancer diagnosis. We sought to create a unifying theory that explains variations in suicide risk across cancer sites, stages, and demographics. Based on the stress-diathesis model, we hypothesized that suicide risk correlates with cancer prognosis and that the impact of prognosis on suicide risk is greatest for populations with higher baseline risks of suicide. Methods: We identified all patients with newly diagnosed cancers from 2000-2019 in the Surveillance, Epidemiology, and End Results (SEER) 17 database, representing 27% of U.S. cancers diagnosed over the past 20 years. Multiple primary-standardized mortality ratios (SMR) were used to determine the relative risk of suicide within the first 6 months compared to the general U.S. population, adjusted for age, sex, race, and year of follow-up. We correlated suicide and 2-year overall survival rates for 20 cancer sites using a weighted linear regression model. Results: We identified 9,046 suicides among 6,811,940 persons diagnosed with cancer, 1,610 of which occurred within 6 months of diagnosis. There were 5.3 suicides per 10,000 person-years, compared with an expected rate of 1.7 (SMR 3.1 [95% CI 3.0-3.3]). Suicide risk correlated strongly with prognosis (increased risk of 9.5% per percent survival deficit at 2 years, R 2 = 0.88, P &lt; .0001). The impact of prognosis on suicide risk was greater for demographic groups with higher baseline risks of suicide. For men, the risk of suicide increased by 3 suicides per 10,0000 person-years (R 2 = 0.84, P &lt; .0001) versus 0.3 in women (R 2 = 0.54, P &lt; .0001). The impact of prognosis on suicide risk was also greater for persons age 60+ and for white (versus black) race. Conclusions: Poorer prognosis correlates with suicide risk in patients with cancer and has a greater effect on populations with higher baseline rates of suicide. Our model should provide a useful framework for triaging patients that need increased surveillance or urgent psychiatric referral.
COVID-19 vaccination in patients with cancer: Results from survey based observational study.
Authors: Hyma Vani Polimera, Lauren Danielle Pomerantz, Emma Guare, Junjia Zhu, Monika Joshi
Journal: Journal of Clinical Oncology (2023)

e18897 Background: COVID‐19 (C19) disproportionately affects those with comorbid medical conditions, leading to significantly higher mortality rate. Cancer(ca) is a well-studied risk factor for developing severe C19 disease. However, ca patients (pts) were largely excluded from clinical trials evaluating the safety and efficacy of 3 FDA-approved C19 vaccines (vax). We aim to study this highly vulnerable pts’ behavior and outcomes regarding C19 vax. Methods: A prospective and observational single center study. Adult ca pts (18-89 years) seen in clinics from Nov 2021-Sept 2022 were randomly interviewed using telephone surveys after a verbal consent. Type of ca and therapy data were collected from pts’ medical records. The survey included C19 disease status, vax status positive (vax+) or negative (vax-), reason for vax status, s.e, impact on ca Rx or ca progression. Our primary objectives were to assess the rate of vaccination in the adult ca pts and identify barriers to vaccination. Secondary objectives were determining factors associated with vax acceptance vs. hesitancy, identifying s.e of C19 vax, and effect of C19 vax on clinical outcomes in ca pts. Results: N = 170 [Males 82 (48.2%) and females 88 (51.8%)]. The median age was 65 years. Among 170 pts, 58.2% had solid malignancy, 40% had hematologic malignancy, and 1.8% had both solid and hematologic malignancy. Refer to Table 1 for outcomes data. Overall, 146 (85.9%) pts received C19 vax. C19 infection positive (C19+) in 49 (28.8%) pts. Of them 9 (18.4%) pts required hospitalization. The vax rate of prior C19+ pts was 73.5% compared to 90.9% in C19 infection negative (C19-) pts (p = 0.0013). Demographic factors were not significantly associated with vaccine uptake. A total of 50% pts developed s.e from vax. However only one patient (0.68%) reported a delay in ca treatment due to C19 vax and believed that vax affected the ca outcome. Conclusions: Our results demonstrate that majority of the ca pts were vaccinated against C19 and tolerated it well, with minimal side effects. Prior C19 infection significantly decreased vax uptake. Vaccination did not have notable adverse effect on ca outcomes. Oncologists should discuss the importance of C19 vax in the context of ca to avoid misconceptions and hesitancy. Clinical trial information: NCT04953065 . [Table: see text]
Synergistic anti-tumor activity of the mTOR inhibitor everolimus and gemcitabine for the treatment of peripheral T cell lymphoma.
Authors: Ling Huang, Fen Zhang, Diwen Pang, Yan Teng, Xinmiao Jiang, Lu Pan, Yichen Sun, Hanguo Guo, Xiaojuan Wei, Feili Chen, Sichu Liu, Caidi Lin, Yali Wang, Ning Wang, Zhanli Liang, Yilan Huang, Choon Kiat Ong, Qingling Zhang, Jing Tan, Wenyu Li
Journal: Journal of Clinical Oncology (2023)

e19538 Background: Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) have dismal prognosis and limited treatment options. The mTOR inhibitor everolimus or gemcitabine as a single agent regimen had limited clinical efficacy in patients with R/R PTCL. Therefore, investigation of active combination therapies with everolimus for T cell lymphoma needs to be investigated. Methods: A retrospective analysis of 24 R/R PTCL patients were treated with everolimus and gemcitabine from December 2017 to March 2021. The primary endpoint was objective response rate (ORR). CellTiter Glo and AnnexinV FITC/PI were utilized to determine cell viability and apoptosis, respectively. Results: Here we demonstrated that combination treatment of everolimus and gemcitabine is effective in treating R/R PTCL patients, achieving an ORR of 70.8%, with 45.8% complete response rate. The median time to response was 1.7 months. With a median follow-up time of 22.3 months (95% confidence interval[CI], 5.7-39.0), the median PFS of all patients was 9.9 months (95%CI, 0-20.81), the median DOR was 16.8 months for responders. Patients with best response of CR and PR achieved superior PFS (18.7 vs. 1.2 months, P = 0.0007) and OS (30.9 vs. 5.8 months, P = 0.021) than that with SD and PD. Grade 3 or 4 neutropenia, thrombocytopenia and anaemia occurred in 13 (29.2% grade 3 and 25.0% grade 4), 11 (8.3% grade 3 and 37.5% grade 4) and 7 (16.6% grade 3 and 12.5% grade 4) patients, respectively. Functional in vitro studies showed that combination treatment synergistically inhibited cell viability and induced apoptosis in PTCL cell lines. Mechanistically, transcriptomic profiling indicated that the synergistic effect was induced through the abrogation of MYC pathway. Conclusions: Collectively, our study sheds light on synergistic antitumor effect of combinatorial therapy, providing a potential therapeutic strategy for patients with R/R PTCL.
The safety of seasonal influenza vaccination among patients prescribed immune checkpoint inhibitors: A self-controlled case series study using administrative data.
Authors: Alicia Ann Grima, Jeff C Kwong, Lucie Richard, Jacques Raphael, Nicole Basta, Alex Carignan, Karin Top, Nicholas Brousseau, Phillip S. Blanchette, Maria Sundaram
Journal: Journal of Clinical Oncology (2023)

6606 Background: Immune checkpoint inhibitor (ICI) therapy for cancer patients carries a risk of severe immune-related adverse events (IRAEs). Since vaccines are immunomodulatory, administering seasonal influenza vaccinations to individuals on ICI therapy may exacerbate this risk. However, these vaccines provide substantial benefit to this at-risk population. As severe IRAEs are rare, previous vaccine safety studies in this population have been underpowered and have shown conflicting results. Methods: We used health administration data on adult Ontarians who initiated ICI therapy and received an influenza vaccine between January 1, 2012, and December 31, 2019. We conducted a self-controlled case series study, with a pre-vaccine control period (12-weeks post-ICI initiation to 14 days before vaccine), risk period (42 days post-vaccine), and a post-vaccine control period (until observation end). Each individual contributed a maximum of 2 years of person-time. Emergency department (ED) visit(s) and/or hospitalization for any cause was used as a surrogate measure of severe IRAE frequency. We fitted a fixed effect Poisson regression model incorporating seasonality and time to estimate incidence. Results: We identified 1133 patients who received an influenza vaccine on ICI therapy. The majority were aged ≥66 years (72.7%), male (62.8%), and had lung cancer (53.9%). A quarter (25.9%) experienced an ED visit and/or hospitalization during the observation period. The rate of ED visits and/or hospitalization per person-days in the risk and control periods were similar, with an incidence rate ratio of 1.04 (95% CI: 0.75, 1.45). Subgroup and sensitivity analyses revealed similar findings. Conclusions: Receipt of a seasonal influenza vaccine was not associated with an increased incidence of ED visit or hospitalization among adults on ICI therapy. The results from this analysis suggest no significant safety concern with administering influenza vaccines to this patient population.
Pancreatic cancer associated ascites: Risk factors, outcomes, and management.
Authors: Justin Dejia Wang, Andrew Eugene Hendifar
Journal: Journal of Clinical Oncology (2023)

e16305 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with significant morbidity and mortality as most patients present with advanced disease. The development of ascites has been associated with poor outcomes and further characterization and contemporary management strategies are needed. Therefore, we performed a comprehensive analysis of PDAC patients with ascites, including clinical and biological data, to describe its incidence, associated clinical factors, and outcomes. Methods: Patients were prospectively consented and enrolled the Gastrointestinal Biobank (“GI-Bank”) at Cedars-Sinai Medical Center, which collected patient specimens, associated clinical data, and self-reported questionnaires. Data was consolidated using a standard software tool (Redcap). Statistical analysis was conducted using Excel and using Datatab.net software tools. Results: Of the 437 patients with PDAC, 182 (41.6%) developed ascites. Overall survival (OS) between ascites and non-ascites groups were significantly different by log-rank test (p = 0.001), and estimated median OS was 473 days (95% CI [407, 537]) in ascites patients versus 554 days [467, 678] in non-ascites patients. In Cox proportional hazards model analysis, ascites status, but not sex or race, was associated with decreased survival (HR 1.49, [1.18, 1.87]). Ascitic fluid data was obtained in 77 patients; 62 (80.5%) had SAAG &gt; 1.1; 14(22.6%) of SAAG &gt; 1.1 patients also had positive cytology. The estimated median OS from the diagnosis of ascites was 100 days [76, 128] and median time to puncture was 4 days. Estimated median time from first tap to death was 56 days [42, 95]. 90 (49.5%) were treated with diuretics and 41 (22.5%) were treated with PleurX catheter. Patients with ascites had a worse survival and were more likely to receive greater than one chemotherapy regimen. There was no relationship between ascites and receipt of surgery or radiation. Conclusions: The development of ascites in patients with pancreatic cancer is common and contributes to significant morbidity and mortality. The use of diuretics is lower than would be expected for patients with elevated SAAG. Prospective evaluation of management strategies is needed to improve this important clinical conundrum.